Catheter-based renal sympathetic nerve denervation on hypertension management outcomes.

Background: Renal sympathetic denervation (RSD) provides a minimally invasive interventional treatment modality for patients with resistant hypertension. However, the post-operative outcomes remain a key area of investigation since its earliest clinical trials.

Aim: To evaluate patient outcomes after RSD intervention among peer-reviewed patient cases.

Treatment of Ruptured Giant Omphalocele and Gastroschisis with Liver Herniation using a Wound Retractor as a Novel Approach.

Ruptured giant omphaloceles (GO) and gastroschisis with total liver herniation are rare cases of exceptionally large abdominal wall defects. Many of these children have lethal outcome. The surgical and postsurgical management are complex.

Renal Denervation Update From the International Sympathetic Nervous System Summit: JACC State-of-the-Art Review.

Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem.

Specific Afferent Renal Denervation Prevents Reduction in Neuronal Nitric Oxide Synthase Within the Paraventricular Nucleus in Rats With Chronic Heart Failure.

Renal denervation (RDN) has been shown to restore endogenous neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) and reduce sympathetic drive during chronic heart failure (CHF). The purpose of the present study was to assess the contribution of afferent renal nerves to the nNOS-mediated sympathetic outflow within the PVN in rats with CHF. CHF was induced in rats by ligation of the left coronary artery.

CNS sites activated by renal pelvic epithelial sodium channels (ENaCs) in response to hypertonic saline in awake rats.

In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis.

Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension.

Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves.

Blockade of ENaCs by amiloride induces c-Fos activation of the area postrema.

Epithelial sodium channels (ENaCs) are strongly expressed in the circumventricular organs (CVOs), and these structures may play an important role in sensing plasma sodium levels. Here, the potent ENaC blocker amiloride was injected intraperitoneally in rats and 2h later, the c-Fos activation pattern in the CVOs was studied. Amiloride elicited dose-related activation in the area postrema (AP) but only ~10% of the rats showed c-Fos activity in the organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO).

Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats.

Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question.

Fos-activation of FoxP2 and Lmx1b neurons in the parabrachial nucleus evoked by hypotension and hypertension in conscious rats.

The parabrachial nucleus (PB) is a brainstem cell group that receives a strong input from the nucleus tractus solitarius regarding the physiological status of the internal organs and sends efferent projections throughout the forebrain. Since the neuroanatomical organization of the PB remains unclear, our first step was to use specific antibodies against two neural lineage transcription factors: Forkhead box protein2 (FoxP2) and LIM homeodomain transcription factor 1 beta (Lmx1b) to define the PB in adult rats. This allowed us to construct a cytoarchitectonic PB map based on the distribution of neurons that constitutively express these two transcription factors.

Angiotensin II and CRF receptors in the central nucleus of the amygdala mediate hemodynamic response variability to cocaine in conscious rats.

Stress or cocaine evokes either a large increase in systemic vascular resistance (SVR) or a smaller increase in SVR accompanied by an increase in cardiac output (designated vascular and mixed responders, respectively) in Sprague-Dawley rats. We hypothesized that the central nucleus of the amygdala (CeA) mediates this variability. Conscious, freely-moving rats, instrumented for measurement of arterial pressure and cardiac output and for drug delivery into the CeA, were given cocaine (5 mg/kg, iv, 4-6 times) and characterized as vascular (n=15) or mixed responders (n=10).

Neurohumoral mechanisms in deoxycorticosterone acetate (DOCA)-salt hypertension in rats.

This brief review describes the role of neural and non-neural mechanisms during different phases of deoxycorticosterone acetate (DOCA)-salt hypertension. There are contradictory data for and against a role of the sympathetic nervous system and neurohumoral agents, including endothelin and vasopressin. Elucidating the factors responsible for DOCA-salt hypertension will be helpful in understanding the causes of hypertension resulting from hypervolaemia, hyperaldosteronism and high salt intake.

Angiotensin and NMDA receptors in the median preoptic nucleus mediate hemodynamic response patterns to stress.

The brain renin-angiotensin system plays an important role in the regulation of arterial pressure in response to stress, in part due to activation of AT1 receptors in the hypothalamic median preoptic nucleus (MnPO) by endogenous angiotensin II (ANG II). N-methyl-d-aspartate (NMDA) receptors are also involved in the angiotensinergic signaling pathway through the MnPO. We investigated whether AT1 and NMDA receptors in the MnPO are responsible for variable hemodynamic response patterns to stress.

Central angiotensin II receptors mediate hemodynamic response variability to stressors.

We examined whether ANG II receptors in the central nervous system mediate hemodynamic responses to pharmacological (cocaine) and behavioral (cold water) stressors. After administration of cocaine (5 mg/kg iv), rats were classified as vascular responders (VR) if their pressor response was due entirely to an increase in systemic vascular resistance (SVR) despite a decrease in cardiac output (CO). Cocaine elicited a pressor response in mixed responders (MR) that was dependent on small increases in both SVR and CO.

Hemodynamics among neonates with hypoxic-ischemic encephalopathy during whole-body hypothermia and passive rewarming.

Objective: To assess changes in cardiac performance, with Doppler echocardiography, among newborns with hypoxic-ischemic encephalopathy during mild therapeutic hypothermia and during rewarming.

Methods: For 7 asphyxiated neonates (birth weight: 1840-3850 g; umbilical artery pH: 6.70-6.

Contribution of baroreflex sensitivity and vascular reactivity to variable haemodynamic responses to cocaine in conscious rats.

1. Baroreflex function is critical for short-term arterial pressure regulation and decreased baroreflex responsivity may predict a predisposition to hypertension and sudden cardiac death. In the present study, we assessed whether baroreflex sensitivity (BRS) and/or vascular reactivity covary with haemodynamic responsiveness to cocaine in vascular and mixed responders.

Central beta-adrenoceptors mediate phasic and sustained components of hemodynamic responses to acute behavioral stress.

Startle elicits a pattern of cardiovascular responses that is consistent within individual rats but varies between rats. We examined the hypothesis that central beta-adrenoceptors mediate differences in the hemodynamic responses to stress. Conscious rats exposed to cold water (1 cm deep, 1 min) had an initial phasic (startle) response (first 5 s) that varied considerably between rats.

Teaching principles of cardiovascular function in a medical student laboratory.

We describe an animal laboratory using anesthetized swine to demonstrate the regulation of arterial blood pressure to second-year medical students at Saint Louis University School of Medicine (St. Louis, MO). The laboratory is designed to illustrate basic pharmacological and physiological concepts learned in the classroom.

Role of angiotensin II and corticotropin-releasing hormone in hemodynamic responses to cocaine and stress.

Cocaine produces characteristic behavioral and autonomic responses due to its unique pharmacological properties. Many of the autonomic responses resemble those to acute behavioral stress. Both cocaine and behavioral stress have been shown to evoke an increase in sympathetic nerve activity that is primarily responsible for the peripheral cardiovascular responses.

Unusual presentation of congenital disorder of glycosylation type 1a: congenital persistent thrombocytopenia, hypertrophic cardiomyopathy and hydrops-like aspect due to marked peripheral oedema.

Unlabelled: Of the congenital disorder of glycosylation (CDG) syndromes, type 1a is the most common. CDG 1a is a multisystem disorder with a wide clinical spectrum. We report on a term newborn with a severe and fatal clinical course of CDG 1a syndrome.

Cocaine enhances susceptibility to endotoxemic shock in a subset of rats.

Objective: We hypothesized that the sympathomimetic cocaine may alter cardiovascular and inflammatory responses and enhance susceptibility to endotoxemia due to innate differences in patterns of sympathetic and cardiovascular responsiveness.

Design: Prospective study.

Setting: Experimental animal laboratory.

Muscarinic cholinergic and beta-adrenergic contribution to hindquarters vasodilation and cardiac responses to cocaine.

Cocaine produces a pressor response associated with an initial hindquarters vasoconstriction followed by a prolonged vasodilation in conscious rats. Propranolol pretreatment prevented the vasodilation and enhanced the pressor response, whereas atropine methylbromide pretreatment reduced the increase in systemic vascular resistance. We studied the role of selective muscarinic and beta-adrenoceptor antagonists on responses to cocaine in rats with an increase in systemic vascular resistance to cocaine (vascular responders).

Central alpha-adrenergic receptors and corticotropin releasing factor mediate hemodynamic responses to acute cold stress.

Behavioral stress is likely to contribute to the development of hypertension in susceptible individuals. We reported that hemodynamic response patterns to acute startle vary and that those patterns predict the predisposition of rats to sustained stress-induced elevations in arterial pressure. Since considerable evidence suggests that central catecholamines and corticotropin releasing factor (CRF) contribute to the regulation of arterial pressure and the development of hypertension, we investigated the role of central alpha-adrenergic receptors and CRF in mediating different hemodynamic response patterns to acute cold water stress in conscious rats.

Hemodynamic response profile predicts susceptibility to cocaine-induced toxicity.

Cocaine evokes pressor responses due either to a large increase in systemic vascular resistance despite a decrease (>8%) in cardiac output (vascular responders) or to small increases in both cardiac output and vascular resistance (mixed responders) in conscious rats. These studies were designed to determine (1) if the hemodynamic response pattern to cocaine correlates with relative sensitivity to toxicity and (2) if altering the hemodynamic response pattern to cocaine using propranolol enhances toxicity. Rats were instrumented for determination of cardiac output and arterial pressure.

Cardiovascular disorders associated with cocaine use: myths and truths.

Cocaine produces a pattern of cardiovascular responses that are associated with apparent myocardial ischemia, arrhythmias, and other life-threatening complications in some individuals. Despite recent efforts to better understand the causes of cocaine-induced cardiovascular dysfunction, there remain a number of unanswered questions regarding the specific mechanisms by which cocaine elicits hemodynamic responses. This review will describe the actions of cocaine on the cardiovascular system and the evidence for the mechanisms by which cocaine elicits hemodynamic and pathologic responses in humans and animals.